A case of Buschke-Löwenstein's tumour presenting with urinary fistula is described. The large lesion in the subpreputial sac occluded the preputial opening and infiltrated beneath the skin of the shaft of the penis resulting in a fungating growth encasing the fistulous tract. The lesion responded well to 25% podophyllin, which is reportedly unusual.
Giant condyloma acuminatum or Buschke-Lowenstein tumour is a very rare disease which usually is located in the genital, anorectal, and perianal regions. It is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces where it is locally invasive but displays a benign cytology. We describe a case of a 24-year-old woman with persisting condyloma acuminata progressing to a large intra-abdominal Buschke-Lowenstein tumour. To our knowledge such an advanced stage has only been reported once before. The severity and extent of the tumour both determine the treatment and patient outcome. Treatment was impeded by cachexia, an immunosuppressive state after kidney transplantation and difficulties in establishing a reliable diagnose. Interferon treatment was started which initially led to tumour reduction but was complicated by an interferon-induced pancreatitis, pneumonia, and fasciitis necroticans resulting in death. We present a literature overview on the treatment options for a Buschke-Lowenstein tumour, with emphasis on interferon therapy, with all the advantages and disadvantages.
Buschke Lowenstein tumour or giant condyloma acuminata is a rare entity with only less then 50 cases reported in English literature so far. No such case has been reported from the Kashmir valley. They are considered as intermediate lesions between simple condyloma acuminata and invasive squamous cell carcinoma. A 57-year-old heterosexual male presented with a giant perianal condyloma. The lesion was surgically excised completely. Postoperatively patient was put on topical 5-FU ointment. Patient is recurrence free 6 months after surgery. The giant condyloma acuminate is an aggressive tumour with propensity for recurrance and malignant transformation. Surgical excision is the treatment of choice. One such rare case is discussed with review of literature.
Condyloma acuminate; Buschke lowenstein; Perianal
Anogenital warts (condyloma acuminatum or venereal warts) are a common sexually transmitted disease in males and females. Common clinical treatment of anogenital warts is conservative, however, in extreme cases conservative therapy is insufficient and surgical excision is required. Giant condyloma acuminata (Buschke-Löwenstein tumour) is an extremely rare clinical type of genital wart, characterised by aggressive down growth into underlying dermal structures. A 55-year-old female presented with cauliflower-like growth over the anogenital and sacral region, earlier diagnosed as condyloma acuminatum which was resistant to conservative therapy. During the period between 2005 and 2008 the patient underwent five surgical procedures. Due to the size and location of the tumour, gynaecological and plastic surgeons were involved in the procedures. In addition, definitive histology examination identified a superficial vulvar carcinoma.
giant condyloma; Buschke-Löwenstein tumour; vulvar carcinoma; surgery
A 48-year-old man presented with multiple warts in groin for 1 year, which progressively increased in size. Local examination showed large vegetative growth in perianal area. Full thickness excision of involved skin and lesions was undertaken by electrocautery. Entire wound was left open to heal by secondary intention. Histopathological examination suggested Buschke-Löwenstein tumour. Postoperative follow-up for more than 2 years showed the absence of any recurrence.
Buschke-Löwenstein tumour; giant condyloma acuminatum; wide radical excision
The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region.
PATIENTS AND METHODS
We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service.
There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery.
The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of preservation and improved survival and this supports the IOG guidance.
Improving Outcomes Guidance; Penis cancer; Penis preservation; Survival
We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman’s theory of neuronal group selection, Changeux’s theory of synaptic selection and selective stabilization of pre-representations, Seung’s Darwinian synapse, Loewenstein’s synaptic melioration, Adam’s selfish synapse, and Calvin’s replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price’s covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise.
neural Darwinism; neuronal group selection; neuronal replicator hypothesis; Darwinian neurodynamics; Izhikevich spiking networks; causal inference; price equation; hill-climbers
Carcinoma cuniculatum of the penis is an extremely rare variant of squamous cell carcinoma characterized by an endophytic deeply branching and burrowing growth pattern. One documented case series demonstrated afflicted patients ranging in age from 73–83 years with the tumour located on the glans penis, coronal sulcus or foreskin. We report a case of a 55-year-old with disease located on the ventral aspect of the shaft of the penis. The tumour was invasive into the deep dermal connective tissue, comparatively superficial to all previous documented cases. He subsequently underwent a partial penectomy. The case is discussed with a brief review of the literature.
A 73-year-old male presented with a 3-month history of two penile masses: one on the shaft and one on the glans penis. Both lesions were poorly defined, fixated and without tenderness. The sizes were 1.0 × 1.0 × 1.0 cm and 1.2 × 1.5 × 1.5 cm, respectively. The patient underwent lumpectomy of the glans penis; we confirmed malignant lymphoma of the glans penis (B-cell derived; diffused large B-cell) by postoperative pathological examinations. CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) chemotherapy was administered. The patient was tumour-free at the 33-month follow-up.
To highlight the salient features of metastatic malignancies involving the penis, with special reference to the primary tumour sites, metastatic mechanisms, clinical features, differential diagnosis, treatment and prognosis.
A comprehensive search of the literature was performed using MEDLINE and EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and 'malignant priapism' to identify reviews and case reports of secondary penile malignancy. A case of rare clinical presentation of metastatic penile lesion is presented along with the review of the literature.
Secondary malignancy of the penis is a rare clinical entity, despite the rich vascularisation of this organ. The majority of metastatic lesions take their origin from the neighbouring genito-urinary organs, mainly prostate and bladder. These lesions are often associated with disseminated malignancy and hence have a poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or priapism are the main modes of clinical presentation. In most cases, only palliative or supportive therapy is indicated.
Cancer of the penis is a rare tumour in Europe and mainly affects the elderly patient population. The aim of this paper was to analyse and study the characteristics of this tumour, in our patient population.
Materials and Methods. A retrospective study was conducted on penile tumours diagnosed and treated in the Urology Department of the Hospital Universitario La Paz, Madrid, in the last ten years.
Results. A total of 34 patients were diagnosed and treated. The mean age at presentation was 71.27 years. The mean time between symptoms and the first consultation was 12.54 months with a median of 6 months. The most common form of presentation was balanoposthitis (32%) and the most common site in our series was the glans. Partial penectomy was performed in 22 cases, total amputation in 8, and local excision in 3. Discussion. Carcinoma of the penis is a pathology which mostly affects elderly patients; in our series, the highest incidence was observed in patients in the group aged 75–84 years. The most common histological type was epidermoid carcinoma in its various forms of presentation. We recorded a mortality of 23%. Conclusion. Penile carcinoma is a rare pathology which affects elderly persons and is diagnosed late.
Verrucous carcinoma of the skin and mucosa is an uncommon type of well-differentiated squamous cell carcinoma. When it is present in the genitoanal region the term used is Buschke-Lowenstein tumor. The human papillomavirus seems to be implicated in its aetiology. Treatment is controversial. Topical chemotherapy, radiotherapy, immunotherapy and radical surgery have been employed.
We report a rapidly progressing penile verrucous carcinoma which was treated sucessfuly with conservative surgery and CO2 laser.
Treatment with CO2 laser in combination with conservative surgery may be a therapeutic option in Buschke-Lowenstein tumor.
condylomata acuminata; lasers; penile neoplasms; squamous cell carcinoma; verrucous carcinoma
Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease.
While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment.
The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found.
Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions.
Paraneoplastic hypercalcemia; Buschke-Löwenstein tumor; Giant condyloma acuminatum
Giant anal condyloma also called Buschke–Löwenstein tumor is a rare sexually transmitted disease involving anogenital region with potential malignant degeneration into invasive squamous carcinoma. Complete surgical excision is the treatment of choice and often wide wounds are necessary to reach clear margins and prevent recurrence.
PRESENTATION OF CASE
The authors present two cases treated with an S-plasty rotating and a bilateral house advancement flap respectively with good functional result.
Giant anal condyloma also called Buschke–Löwenstein tumor is a large exophytic, cauliflower-like mass that is characterized by local aggressive behavior. Immunosuppression favors rapid growth of the condylomas and increases the risk of their malignant transformation. In limited lesions primary excision can be safely performed leaving wounds open to granulate while in more extensive lesions flap or skin graft coverage is preferable to decrease the length of recovery and minimize risk of severe anal stricture. Abdominoperineal resection should be performed for more extensive lesions with deep invasion, malignant transformation or tumor recurrence.
Giant anal condyloma also called Buschke–Löwenstein is a rare pathology with mainly sporadic single center experience reported in literature. Surgical complete excision remains the best treatment although elevate should be eventual recurrence. No sufficient data are available to recommend any medical treatment such as interferon, radiotherapy or chemotherapy.
Giant condyloma; Buschke–Löwenstein tumor; S-plasty rotating flap; House advancement flap
Fibroepithelial polyps are rare benign tumours of the glans penis; there are only a few reported cases. The pathogenesis is unknown. However, they have been linked with chronic condom catheter use or prior penile surgery. We report a case of a 62-year-old man with a large fibroepithelial polyp of the glans penis of 11 years duration, which was not associated with condom catheter use or prior surgery. The mass was large, measuring 7 × 5 × 3 cm. Fibroepithelial polyps have been reported in a range of genito-urinary sites in males and females, adults and children, and in rare cases may be associated with malignant transformation. They should be considered in the differential diagnosis of both cutaneous and mucosal genitourinary lesions.
The permeability of junctions between cells of the same type (homologous junctions) is greatly increased by retinoic acid (10(-9)- 10(-8) M), a probable morphogen, and this responsiveness is shared by a variety of normal and transformed cell types (Mehta, P.P., J.S. Bertram, and W.R. Loewenstein. 1989. J. Cell Biol. 108:1053-1065). Here we report that the heterologous junctions between the normal and transformed cells respond in the opposite direction; their permeability is reduced by retinoic acid (greater than or equal to 10(-9) M) and its benzoic acid derivative tetrahydrotetramethylnaphthalenylpropenylbenzoic acid (greater than or equal to 10(-11) M). The opposite responses of the two classes of junction are shown to be concurrent; in cocultures of normal 10T1/2 cells and their methylcholanthrene-transformed counterparts, the permeability of the heterologous junctions, which is lower than that of the homologous junctions to start with, falls (within 20 h of retinoid application), at the same time that the permeability of the homologous junctions rises in both cell types. Such a counter-regulation requires a minimum of three degrees of cellular differentiation. A model is proposed in which the differentiations reside in a trio of junctional channel protein. The principle of the model may have wide applications in the regulation of intercellular communication at tissue boundaries, including embryonic ones.
People have present-biased preferences: they choose more impatiently when choosing between an immediate reward and a delayed reward, than when choosing between a delayed reward and a more delayed reward. Following McClure et al. [McClure, S.M., Laibson, D.I., Loewenstein, G., Cohen, J.D. (2004). Separate neural systems value immediate and delayed monetary rewards. Science, 306, 503.], we find that areas in the dopaminergic reward system show greater activation when a binary choice set includes both an immediate reward and a delayed reward in contrast to activation measured when the binary choice set contains only delayed rewards. The presence of an immediate reward in the choice set elevates activation of the ventral striatum, pregenual anterior cingulate cortex and anterior medial prefrontal cortex. These dopaminergic reward areas are also responsive to the identity of the recipient of the reward. Even an immediate reward does not activate these dopaminergic regions when the decision is being made for another person. Our results support the hypotheses that participants show less affective engagement (i) when they are making choices for themselves that only involve options in the future or (ii) when they are making choices for someone else. As hypothesized, we also find that behavioral choices reflect more patience when choosing for someone else.
present-biased preferences; intertemporal discounting; fMRI; multiple systems hypothesis
Extrapulmonary tuberculosis (EPTB) is defined as Mycobacterium TB through Ziehl–Neelsen acid-fast stain and culture in Loewenstein–Jensen in a tissue from a site other than lung parenchyma, in association with clinical or imaging findings compatible with infection locally. The authors report a case of a patient who presented with asthenia, anorexia and weight loss. He complained of fever, chills and night sweats of 1-week duration. The thoracic scan reveals lymph node enlargement in the left axilla and pleural effusion and the histological study revealed a necrotising granulomatous lymphadenitis. It was decided to initiate antituberculous drugs with a good response. EPTB is a difficult diagnostic because lymph nodes contain few tubercle bacilli, leading to a low sensitivity of smear microscopy detection. The introduction of antituberculous agents is the cornerstone of management of such infections and, occasionally, it is the only way to make a diagnosis.
The prospective project MOSAR was conducted in five rehabilitation units: the Berck Maritime Hôpital (Berck, France), Fondazione Santa Lucia (Rome, Italy), Guttmann Institute (GI; Barcelona, Spain), and Loewenstein Hospital and Tel-Aviv Souraski Medical Center (TA) (Tel-Aviv, Israel). Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins (ESCs) from admission until discharge. The aim of this study was to characterize the clonal structure, extended-spectrum β-lactamases (ESBLs), and acquired AmpC-like cephalosporinases in the Escherichia coli populations collected. A total of 376 isolates were randomly selected. The overall number of sequence types (STs) was 76, including 7 STs that grouped at least 10 isolates from at least three centers each, namely, STs 10, 38, 69, 131, 405, 410, and 648. These clones comprised 65.2% of all isolates, and ST131 alone comprised 41.2%. Of 54 STs observed only in one center, some STs played a locally significant role, like ST156 and ST393 in GI or ST372 and ST398 in TA. Among 16 new STs, five arose from evolution within the ST10 and ST131 clonal complexes. ESBLs and AmpCs accounted for 94.7% and 5.6% of the ESC-hydrolyzing β-lactamases, respectively, being dominated by the CTX-M-like enzymes (79.9%), followed by the SHV (13.5%) and CMY-2 (5.3%) types. CTX-M-15 was the most prevalent β-lactamase overall (40.6%); other ubiquitous enzymes were CTX-M-14 and CMY-2. Almost none of the common clones correlated strictly with one β-lactamase; although 58.7% of ST131 isolates produced CTX-M-15, the clone also expressed nine other enzymes. A number of clone variants with specific pulsed-field gel electrophoresis and ESBL types were spread in some locales, potentially representing newly emerging E. coli epidemic strains.
Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined.
Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols.
Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001).
These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.
We have reported the molecular cloning, expression, and characterization of a human cellular protein, TAP, which possesses a strong transcriptional activation domain and binds the human immunodeficiency virus type 1 Tat transactivator in vitro and in vivo (L. Yu, Z. Zhang, P.M. Loewenstein, K. Desai, Q. Tang, D. Mao, J.S. Symington, and M. Green, J. Virol. 69:3007-3016, 1995). Here we show that TAP binds the general transcription factor TFIIB. Furthermore, we delineate the binding domains of TAP, Tat, and TFIIB, as well as measure the strengths and specificity of these protein-protein interactions. TAP binds strongly to Tat, with a Kd of (approximately 2 to 5) x 10(-7) M. The Tat activation region contains a 17-amino-acid conserved core domain which is the single contact site for TAP. Single-amino-acid substitutions within the Tat core domain inactivate transactivation in vivo and in vitro and greatly reduce binding of Tat to TAP in vitro. TAP binds strongly to TFIIB, with about the same Kd as for Tat. The interaction between TAP and TFIIB requires a sequence near the carboxy terminus of TFIIB which is also required for binding the strong acidic activator VP16. The contact sites for Tat and TFIIB map within the TAP C-terminal region, which contains the TAP activation domain. These combined results are consistent with the hypothesis that TAP is a cellular coactivator that bridges the Tat transactivator to the general transcription machinery via TFIIB.
Neonatal circumcision is widely considered to have a protective effect against the development of squamous cell carcinoma of the penis in later life. We report 3 cases of squamous cell carcinoma in men who were circumcised as neonates. The 3 men, aged 49, 55 and 64 years, presented for consideration of brachytherapy. The tumour stage was T3 in 1 case and T1 in the others. The tumours were moderately differentiated in 2 cases and well differentiated in 1 case. All 3 men had a remote history of penile condylomata acuminatum 20–30 years earlier. Oncogenic human papillomavirus (HPV) was found in the tumour specimen in 1 case. All 3 were treated with brachytherapy to the primary tumour on the glans. In 2 cases, subsequent staging inguinal node dissection was indicated because of the grade and stage of the primary tumour. A history of remote HPV infection should increase the index of suspicion for any nonhealing penile lesion, despite a history of neonatal circumcision.
Leiomyomas are benign tumours that originate from smooth muscles. They are often seen in the uterus, but also in the renal pelvis, bladder, spermatic cord, epididymis, prostate, scrotum or the glans penis. Leiomyomas of the tunica albuginea are extremely rare.
A 59-year-old white male has noted an asymptomatic tumour on the right side of his scrotal sac for several years. This tumour has increased slowly and caused local scrotal pain. An inguinal incision was performed, in which the hypoplastic testis, the epididymis and the tumour could be easily mobilized. Macroscopically the tumour showed a solid round nonencapsulated whorling cut surface. Histologically the diagnosis of a leiomyoma was made.
We report here a very interesting and rare case of a leiomyoma of the tunica albuginea. Leiomyomas can be a possible differential diagnosis in this area.
Leiomyoma; Tunica albuginea; Immunohistochemistry
We present a case of a symplastic or "bizarre" leiomyoma of the scrotum. Isolated cases of leiomyomas have been reported arising from the renal pelvis, bladder, spermatic cord, epididymis, prostate as well as the glans penis. However such mesenchymal lesions of the scrotum are very rare.
Macroscopically the tumour was a well-circumscribed grey-white lesion 8.5 cm in size. Because of its peculiar histological characteristics this tumour was assigned as a symplastic or bizarre leiomyoma of the scrotum.
We present this unusual tumour and highlight some important diagnostic and treatment pitfalls related to this rare tumour. This case demonstrates that leiomyomas should be considered in the differential diagnosis of scrotal tumours.